Anthrax vs. Cancer – Researchers Harness Deadly Toxin to Cure Dogs and Potentially People
Dogs with terminal bladder cancer improved with a new modified anthrax treatment. pyotr021 / iStock / Getty Images Plus
By R. Claudio Aguilar
Can the feared anthrax toxin become an ally in the war against cancer? Successful treatment of pet dogs suffering bladder cancer with an anthrax-related treatment suggests so.
Anthrax is a disease caused a by bacterium, known as Bacillus anthracis, which releases a toxin that causes the skin to break down and forms ulcers, and triggers pneumonia and muscle and chest pain. To add to its sinister resumé, and underscore its lethal effects, this toxin has been infamously used as a bioweapon.
I am a biochemist and cell biologist who has been working on research and development of novel therapeutic approaches against cancer and genetic diseases for more than 20 years. Our lab has investigated, designed and adapted agents to fight disease; this is our latest exciting story.
Among all cancers, the one affecting the bladder is the sixth most common and in 2019 caused more than 17,000 deaths in the U.S. Of all patients that receive surgery to remove this cancer, about 70% will return to the physician's office with more tumors. This is psychologically devastating for the patient and makes the cancer of the bladder one of the most expensive to treat.
To make things worse, currently there is a worldwide shortage of Bacillus Calmette-Guerin, a bacterium used to make the preferred immunotherapy for decreasing bladder cancer recurrence after surgery. This situation has left doctors struggling to meet the needs of their patients. Therefore, there is a clear need for more effective strategies to treat bladder cancer.
Anthrax Comes to the Rescue
Years ago scientists in the Collier lab modified the anthrax toxin by physically linking it to a naturally occurring protein called the epidermal growth factor (EGF) that binds to the EGF receptor, which is abundant on the surface of bladder cancer cells. When the EGF protein binds to the receptor – like a key fits a lock – it causes the cell to engulf the EGF-anthrax toxin, which then induces the cancer cell to commit suicide (a process called apoptosis), while leaving healthy cells alone.
In collaboration with colleagues at Indiana University medical school, Harvard University and MIT, we designed a strategy to eliminate tumors using this modified toxin. Together we demonstrated that this novel approach allowed us to eliminate tumor cells taken from human, dog and mouse bladder cancer.
This highlights the potential of this agent to provide an efficient and fast alternative to the current treatments (which can take between two and three hours to administer over a period of months). I also think it is good news is that the modified anthrax toxin spared normal cells. This suggests that this treatment could have fewer side effects.
Helping Our Best Friends
These encouraging results led my lab to join forces with Dr. Knapp's group at the Purdue veterinary hospital to treat pet dogs suffering from bladder cancer.
Canine patients for whom all available conventional anti-cancer therapeutics were unsuccessful were considered eligible for these tests. Only after standard tests proved the agent to be safe in laboratory animals, and with the consent of their owners, six eligible dogs with terminal bladder cancer were treated with the anthrax toxin-derived agent.
Two to five doses of this medicine, delivered directly inside the bladder via a catheter, was enough to shrink the tumor by an average of 30%. We consider these results impressive given the initial large size of the tumor and its resistance to other treatments.
There Is Hope for All
Our collaborators at Indiana University Hospital surgically removed bladder cells from human patients and sent them to my lab for testing the agent. At Purdue my team found these cells to be very sensitive to the anthrax toxin-derived agent as well. These results suggest that this novel anti-bladder cancer strategy could be effective in human patients.
The treatment strategy that we have devised is still experimental. Therefore, it is not available for treatment of human patients yet. Nevertheless, my team is actively seeking the needed economic support and required approvals to move this therapeutic approach into human clinical trials. Plans to develop a new, even better generation of agents and to expand their application to the fight against other cancers are ongoing.
R. Claudio Aguilar is an associate professor of biological sciences at Purdue University.
Disclosure statement: R. Claudio Aguilar received funding from National Institutes of Health.
Reposted with permission from The Conversation.
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Association Versus Intervention Studies<p>Many studies on the vitamin are association or observational studies. "By definition, these studies cannot prove the causal relationship, but only point to mere correlations," said Fassnacht. The physician tries to illustrate this with an example:</p><p>"Imagine two groups of 80-year-olds. One group is spry, active and does sports. If you compare them with another group living in nursing homes, the difference in vitamin D levels will be dramatic. Life expectancy would also be extremely different."</p><p>But to try to explain the difference in fitness by vitamin D status alone is far too simplistic. "Vitamin D levels are a good measure of how sick someone is. But not more," says Fassnacht. </p><p>According to Fassnacht, none of the intervention studies carried out to date -- that specifically examined the effect of vitamin D on various diseases -- has been able to confirm the previous association and laboratory studies or the presumed positive effect of vitamin D.</p>
Further Research Is Needed<p>"If a coronavirus infection is suspected, it is therefore absolutely necessary to check the vitamin D status and quickly correct any possible deficit," said the recommendation of the paper published by the University of Hohenheim.</p><p>"Studies are underway to see whether vitamin D helps in COVID-19 infection, but I personally do not believe that this is really the case," says endocrinologist Fassnacht. Nevertheless, he says it is of course useful to carry out these studies.<br></p><p>"I don't want to rule out that there are actually subgroups of people who benefit from an additional vitamin D dose," he says. After all, this has been proven to be the case with a severe deficit.</p><p>In view of the study situation, Fassnacht does not think much of preventive, nationwide vitamin D substitutes. "My belief that the vitamin helps somewhere is very low. But, of course, I can be wrong."</p>
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